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The Houston Astros will go for the series sweep when they meet the San Diego Padres in the third and final game of their interleague series on Sunday Night Baseball. Houston opened with a 6-4 win on Friday and followed that up with a 3-2 victory on Saturday. The Padres (15-6), who lead the National League West, are just 3-5 on the road this season. The Astros (10-10), fourth in the American League West, are 6-5 on their home field.

First pitch from Daikin Park in Houston is set for 7:10 p.m. ET. Houston is a -118 favorite on the money line (risk $118 to win $100) in the latest Padres vs. Astros odds from DraftKings Sportsbook, while the over/under, or total number of runs Vegas thinks will be scored, is 7.5. Before making any Padres vs. Astros picks, be sure to see the MLB predictions from SportsLine’s proven model.

The SportsLine Projection Model simulates every MLB game 10,000 times. It enters Week 4 of the 2025 MLB season on an 8-3 run MLB money-line betting picks (+340). Anybody following at sportsbooks and on betting apps could have seen strong returns.

Now, here are the model’s three best bets for Padres vs. Astros on Sunday:

Astros to win (-118)

Houston has won two games in a row for the first time this season and sports a 6-5 record at home. Despite San Diego’s hot start to the season and best record in baseball, the Padres are just 3-5 on the road in 2025. The Astros have also had San Diego’s number in games played at Houston, winning the last four meetings there. Astros pitching has limited the long ball so far in 2025, allowing just 18 home runs, fourth-best among American League teams. DraftKings Sportsbook has the best price on the Astros winning at -118.

If you want even more MLB picks, SportsLine’s top MLB expert, Matt Severance, is heating up. Get his best bets for Saturday, all from the expert who is 58-27 on his last 85 MLB picks (+1494). 

Under 7.5 total runs (-105)

Both teams will send their aces to the mound. Left-hander Framber Valdez (1-2, 4.91 ERA) is expected to get the start for Houston. He has flip-flopped good and bad outings in his previous four starts this season. In a no-decision in a 2-1 win at Seattle on April 8, he pitched six innings, allowing two hits, no runs and one walk, while striking out eight. San Diego is expected to send right-hander Dylan Cease (1-1, 6.64 ERA) to the mound. He was a 14-game winner a year ago with a 3.47 ERA in 33 starts for the Padres.

The teams have combined to score seven or fewer runs in four of their previous five meetings. The model gives just two San Diego batters at least a 43% chance for an RBI, including Manny Machado and Fernando Tatis Jr. Five Houston players were given at least a 42% chance of knocking in a run – Yordan Alvarez, Christian Walker, Isaac Paredes, Cam Smith and Yainer Diaz. The model is projecting 7.9 combined runs, as the under hits in over 50% of simulations.

You’ve now seen two best bets for Padres vs. Astros on Sunday. Now, get picks for every single game from the model that enters Week 4 of the 2025 MLB season on an 8-3 run on top-rated MLB run-line picks.

Total hits for both teams over 15.5 (+105)

With Valdez and Cease squaring off, the model still says the pitching staffs will combine to allow 16 hits. Valdez allowed 10 hits in his last outing, an 8-3 loss at St. Louis on Monday, while Cease gave up seven hits in Monday’s win over the Cubs. Cease also allowed nine hits in a 10-4 loss to the Athletics on April 8. DraftKings has this prop at +105.